title: Bivalent bendamustine and melphalan derivatives as anticancer agents.
abstract: The alkylating agents bendamustine and melphalan are currently used in the treatment of various tumoral diseases. In order to increase their antitumor potency and tumor selectivity both compounds were integrated in structure-activity relationship studies including new drug carrier systems. Here we describe the synthesis and the cytotoxicity of new bivalent bendamustine and melphalan derivatives. Two molecules each esterified with N-(2-hydroxyethyl)maleimide were connected by diamines with various chain lengths (n=6, 7, 8, 12). It was supposed that these conjugates (5a-d, 10a-d, 11a-d) cause cytotoxic effects preferred as bivalent drug. Indeed the cytotoxicity of the new compounds increased compared to bendamustine and melphalan as determined in concentration-dependent in vitro assays using the human MCF-7 and MDA-MB-231 breast cancer cell lines.
authors.affiliation: Institute of Pharmacy, Freie Universität Berlin, Königin Luise Str. 2+4, 14195 Berlin, Germany.
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Scutaru
authors.forename: Maxi
authors.initials: M
authors.lastname: Wenzel
authors.forename: Ronald
authors.initials: R
authors.lastname: Gust
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000069461:Bendamustine Hydrochloride; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008558:Melphalan / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D009588:Nitrogen Mustard Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D009588:Nitrogen Mustard Compounds; D000069461:Bendamustine Hydrochloride; D008558:Melphalan